Although many medical conditions are satisfactorily treated by the general systemic administration of a therapeutic agent, the treatment of many conditions require delivery of the therapeutic agent locally within a body vessel and/or to a selected portion of internal body tissue, without systemic delivery of the therapeutic agent and/or minimizing delivery of the therapeutic agent to surrounding tissue. A systemically administered therapeutic agent may be absorbed not only by the tissues at the target site, but also by other areas of the body. As such, one drawback associated with the systemic administration of therapeutic agents is that areas of the body not needing treatment can also be affected.
Medical delivery catheters provide a minimally invasive means for delivering therapeutic agents to internal body tissue. To provide site-specific localized treatment, balloon catheters may be used to deliver a therapeutic agent directly to the target site within a body vessel. One example of a condition that is beneficially treated by local administration of a therapeutic agent with a balloon catheter is the delivery of a therapeutic agent in combination with percutaneous transluminal coronary angioplasty (PTCA), a technique used to dilate stenotic portions of blood vessels. In such cases, a catheter balloon coated with the therapeutic agent is positioned at a blocked lumen or target site during PTCA, and the balloon is inflated causing dilation of the lumen. The catheter balloon is pressed against the vessel wall for ideally rapid release and absorption of the therapeutic agent by the vessel wall. The balloon is deflated and the catheter is then removed from the target site and the patient's lumen thereby allowing blood to more freely flow through the now less restricted lumen.
Although PTCA and related procedures aid in alleviating intraluminal constrictions, such constrictions or blockages may reoccur in many cases. The cause of these recurring obstructions, termed restenosis, may be due to the body responding to the surgical procedure. Restenosis of the artery may develop over several months after the procedure, and may require another angioplasty procedure or a surgical by-pass operation to correct. Proliferation and migration of smooth muscle cells (SMC) from the media layer of the lumen to the intimal layer cause an excessive production of extra cellular matrices (ECM), which is believed to be one of the leading contributors to the development of restenosis. The extensive thickening of tissues narrows the lumen of the blood vessel, constricting or blocking the blood flow through the vessel. Therapeutic agents selected to limit or prevent restenosis may be locally delivered during PTCA from a catheter and/or by placement of a stent configured to continue to release the therapeutic agent after the PTCA procedure. Catheter balloons may be used in combination with stents, synthetic vascular grafts or drug therapies, during the PTCA procedure to reduce or eliminate the incidence of restenosis.
In addition, balloon catheters can be coated with a coating solution including more than just the therapeutic agent. Various configurations of the solution including the therapeutic agent can be applied to the outer surface of the catheter balloon. In preparation of the drug coating solution, several ingredients, such as a therapeutic agent, a contrast agent, an additive, a solvent, and/or others, are mixed and then applied to the catheter balloon. However, this can be problematic. Often, the physical characteristics of these coatings, such as solubility, integrity, and uniformity of the coating, are undesirable. For instance, a result of the added ingredients to the therapeutic agent can unacceptably increase the solubility of the therapeutic agent to the point where, during translation of the balloon catheter to the target site, a substantial portion of the drug coating can wash away in the vessel downstream, leaving a less effective amount for treatment after reaching the target site. Also, the more contrast media mixed with the therapeutic agent results in less crystalline therapeutic agent (i.e., less durable), which can cause the formation of clumps in the coating that can easily flake off during handling or delivering of the balloon catheter. Consequently, there is a high variability in its effectiveness, i.e., inconsistent therapeutic effects, due to these deficiencies, which adversely affects the uniformity and consistency of the drug delivery to the target site.
Other balloon catheter devices have been developed to administer a therapeutic agent locally to tissue while dilating a body vessel, such as during delivery of a therapeutic agent to a dilated portion of a coronary artery during a PTCA procedure. For instance, a therapeutic agent may be administered directly to the target site through small holes or apertures in the wall of a catheter balloon. Other examples include dual balloon catheters for the application of a therapeutic agent to a blood vessel wall. The distal portion of the dual balloon catheter includes an inner balloon enclosed by a porous outer balloon. In operation, a therapeutic agent may be administered through a lumen in communication with the annular space between the inner and the outer balloon in the catheter, and released through an array of minute holes or micropores in the outer balloon as the therapeutic agent flows into the space between the balloons through a lumen in the catheter shaft. The therapeutic agent is released by the action of pressurization in the lumen in communication with the outer balloon and forced out of the holes or micropores. With these dual balloon catheters, the clinician typically has to choose the therapeutic agent and pre-mix the therapeutic agent with a contrast media (e.g., 50/50 mix) at the bedside of the patient, and then introduce the mixture to the dual balloon catheter for administration to the target site.
Thus, what is needed is a drug coated balloon catheter that facilitates delivery of a therapeutic agent to a body vessel wall more uniformly and consistently. Further, what is needed is a drug coated balloon catheter that rapidly delivers more consistently a therapeutically effective amount of drug to a body vessel wall. It would also be desirable to provide the clinician a dual balloon catheter for delivering a therapeutic agent, without the additional steps of measuring and mixing the therapeutic agent at the bedside of a patient.